Cannabis use may play a causal role in the development of psychotic disorders, including schizophrenia, new research suggests

In a meta-analysis of more than 80 studies, investigators found that the mean age at illness onset was more than 2.5 years earlier for cannabis users compared with nonusers. However, age of onset did not significantly differ between alcohol users and nonusers.

"I was surprised by the strength of the finding and the seemingly specific result for cannabis and not for alcohol," lead author Matthew Large, MBBS, Department of Mental Health Services at Prince Wales Hospital and the School of Psychiatry at the University of New South Wales in Sydney, Australia, told Medscape Medical News.

"The study's message for cannabis smokers, in particular young cannabis smokers, is that there are real risks associated with its use," said Dr. Large.

The investigators note that decreasing this use could delay or even prevent some cases of psychosis.

"Reducing the use of cannabis could be one of the few ways of altering the outcome of the illness because earlier onset of schizophrenia is associated with a worse prognosis and because other factors associated with age at onset, such as family history and sex, cannot be changed," they write.

"The results of this study confirm the need for a renewed public health warning," the investigators add.

The study was published online February 7 in the Archives of General Psychiatry.

Earlier Onset

According to the study, cannabis is the most widely used addictive substance after tobacco and alcohol. It is estimated that more than 16 million Americans are regular users.

Although previous research has shown that substance use is more common in patients with a psychotic disorder compared with the general population, "not all researchers agree that the association between cannabis use and earlier age at onset is causal," the investigators report.

"I am a clinician working almost exclusively with people with psychotic disorders. And substance abuse is a pressing and immediate problem," said Dr. Large.

"Questions have remained about the association between cannabis and psychosis. It has both theoretical implications for the cause of schizophrenia and a potential public health message," he added.

For this analysis, the investigators evaluated data on 83 English-language studies that compared the age of psychosis onset in patients who used substances other than tobacco (n = 8; 167 total) with those who did not (n = 14,352)

Patients who used substances were further divided into 3 subgroups: use of alcohol alone, use of cannabis alone, or use of unspecified substances.

Results showed that the cannabis users' onset of psychosis occurred 2.70 years earlier than onset for nonusers (P < .001). For those who used substances that were unspecified, the age at onset was 2 years younger than for nonusers (P < .001).

These findings "support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients [and] confirm the need for further neurobiological research," write the investigators.

They note that the study questions whether this finding is triggered by "direct neurotoxic effects, by alternations in dopamine activity, or by other changes in neurotransmission."

"Even if the onset of psychosis was inevitable, an extra 2 or 3 years of psychosis-free functioning could allow many patients to achieve the important developmental milestones of late adolescence and early adulthood that could lower the long-term disability arising from psychotic illness."